What Uganda is teaching us about cancer

Fred Hutch-Uganda alliance builds a new cancer center on the shoulders of giants

May 12, 2015

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By Mary Engel / Fred Hutch News Service

"It's been a long, long journey here," said Dr. Fred Okuku, a Ugandan who trained at the Uganda Cancer Institute. "All those things we talked about ... and thought would never come to pass – are now here."

Photo by Robert Hood / Fred Hutch News Service

Editor's note: Fred Hutch News Service writer Mary Engel and photographer Robert Hood were in Uganda for the May 21 grand opening of the UCI-Fred Hutch Cancer Centre. To read more of Mary and Robert's stories from Uganda, please click here.

When he arrived in Kampala, Uganda, in 1969, Dr. Mac Cheever was a 25-year-old medical student with an interest in infectious diseases and an urge to see Africa. Cobbling together a three-month elective at the University of Michigan Medical School with three months of vacation, he planned to do research on the parasitic disease schistosomiasis. Instead, he found himself working at the then two-year-old Uganda Cancer Institute alongside rock-star U.S. and British scientists — and discovered a lifelong passion for cancer research.

“I was so fascinated by what they were doing I asked to be their intern,” he said. “I wouldn’t have gone into cancer if I hadn’t gone to Uganda.”

Now an accomplished researcher at Fred Hutchinson Cancer Research Center and principal investigator for the national Cancer Immunotherapy Trials Network, Cheever will return to Kampala for the first time since his medical school days for the opening of the UCI-Fred Hutch Cancer Centre on May 21.

The three-story, state-of-the-art research, training and outpatient facility — the first comprehensive cancer center jointly built by U.S. and African cancer institutions in sub-Saharan Africa — is the fruit of an alliance with the UCI begun in 2004 by Fred Hutch Global Oncology Director Dr. Corey Casper.

But its roots go back farther than that — to an Irish surgeon whose work in Kampala in the 1950s put Uganda on the cancer research map and in the 1960s excited the interest and investment of the U.S. National Cancer Institute. And they go back to the Ugandan physicians and nurses who kept the UCI open through the dark decades of political upheaval and violence that followed that first flowering until a new alliance and — now a new building — restored hope for cancer care in East Africa.

‘Curing Burkitt lymphoma was like magic’

In Kampala in 1969, Cheever saw something that was then still rare: physician-scientists were curing cancer with chemotherapy. At the time, surgery and radiation were still the dominant cancer therapies in the U.S. No wonder he was fascinated.

One patient he remembers well was a little girl named Nabakoza, whose jaw was horribly swollen from Burkitt lymphoma. This rapidly fatal cancer of the immune system — the most common cause of childhood cancer deaths in sub-Saharan Africa — was first described in 1958 by Dr. Denis Burkitt, an Irish surgeon and missionary working in Kampala when Uganda was still a British protectorate. Over the years and working with other scientists internationally, Burkitt found first one and then a combination of drugs that melted the tumors away. It was the first successful use of combination chemotherapy to cure cancer.

Dr. Denis Burkitt, an Irish surgeon and missionary working in Uganda in the late '50s, pioneered the first successful use of combination chemotherapy to cure cancer.

Photo by Getty Images

After Burkitt published a second paper in 1961 and also began to travel and lecture widely, the world began to take notice of what was happening in Uganda.

In addition to describing and developing treatment for this childhood lymphoma, Burkitt mapped the cancer’s distribution. He found it in areas with warm temperatures, high rainfall and high malaria rates, and wondered if it was infection-related. Using tumor samples provided by Burkitt, British researcher Dr. Anthony Epstein in 1964 identified a new herpes virus, now called Epstein-Barr, which led to a growing recognition that infections are associated with nearly one-quarter of cancer cases around the world, including those of the cervix, liver and stomach.

In 1965, the NCI, which was deeply involved in chemotherapy research, partnered with Kampala’s prestigious Makerere University and began supplying funding and researchers. With support from the NCI and under the leadership of Dr. John Ziegler, an NCI-trained physician-scientist, the Lymphoma Treatment Centre — the forerunner of what would become the Uganda Cancer Institute — opened.

When Cheever arrived two years later, he witnessed firsthand the dawn of the age of chemotherapy. Nabakoza, the little girl with the jaw tumor, had a mass so large she needed a tracheostomy to breathe. On the day she was given her first dose of intravenous cyclophosphamide, Cheever and NCI physicians took turns staying up with the child through the night.

Within 24 hours, the tumor had shrunk perceptibly. With more treatments, it disappeared entirely, and the child went home.

“This was a time when chemotherapy was not effective, and they were curing patients with cyclophosphamide,” Cheever said in a recent interview in his Fred Hutch office. “You’d come in the next day and the tumor would be smaller. It would be gone in a week. Seeing these big tumors just go away — it was phenomenal.”

Marissa Mika, an anthropologist who did her dissertation on the history of the UCI and who will be teaching African history this fall at the University of San Francisco, understands why the case still stands out so clearly to Cheever 46 years later.

“Curing Burkitt lymphoma was like magic,” she said. “There was nothing like it in oncology at the time.”

Idi Amin and years of upheaval

Uganda became independent in 1962, and U.S. and Ugandan cancer researchers enjoyed a stable relationship at first under the country’s new government. Between 1967 and 1976, the UCI was run on contract between the NCI and Makerere University in Kampala. Cheever was in Seattle by then, his work in Uganda having helped secure a fellowship at the University of Washington. But physician-scientists working in Kampala continued to make discoveries and to improve care.

Then, in 1971, Gen. Idi Amin seized power and instituted a reign of terror. Among the 300,000 people he is estimated to have ordered killed were cabinet ministers, Supreme Court judges, diplomats, university administrators – and hospital directors and surgeons. In 1972 — the same year that Burkitt, Ziegler and two other physician-scientists received prestigious Lasker awards for their work in Uganda — U.S. and British researchers withdrew from the country due to threats against their safety.

The long-term plan had been to turn over direction of the center to an all-Ugandan staff, and Dr. Charles Olweny, a Ugandan oncologist and researcher, was being mentored at the NCI in the U.S. for the job. Olweny was halfway through a two-year training program when he received the call to return home.

“The message I received was, ‘Better come back now. If you do not, there will be nothing to return to,’” Olweny — today the chairman of the UCI board — told a reporter in 2012.

Mika, the historian, noted that, despite the political and economic crises that devastated Uganda, Olweny continued to treat patients, conduct clinical trials on treating Burkitt lymphoma with chemotherapy and publish five or six papers a year.

Former NCI director Dr. Harold Varmus, a Nobel laureate and longtime advocate of global cancer research, recently wrote a brief history of medical research in Uganda for a series of lectures on science and diplomacy. “A central feature of the UCI – and a strong determinant of its success,” he wrote, “has been the excellence of its Ugandan physician-leaders, especially in times of political upheaval.”

The NCI continued to funnel money to the UCI until 1977, according to Varmus. After that, Olweny managed to obtain some money for drugs and salaries from the Ugandan Health Ministry. But under Amin and during the succession battles that followed his ouster, threats to Olweny’s life circulated. He left the country in 1982 and continued his research career in exile in Zimbabwe, Australia and Canada.

Dr. Edward Mbidde took over as director and for the next two decades was the sole oncologist in a country of more than 30 million people. The UCI was folded into the much-larger Mulago National Referral Hospital and, operating during periods of great scarcity and disruption, provided mainly palliative care. The political situation stabilized after 1986 under President Yoweri Museveni, who continues in power today. But then Uganda was hit hard by the AIDS epidemic, and with it, a surge in AIDS-related cancers such as Kaposi sarcoma.

‘The place looked like it had no future’

The underfunded UCI struggled to keep up. Beds were jammed into every available space, with pallets on the floor. After so many hard years, the aging wards had fallen into disrepair. Drugs and supplies as basic as gloves were few.

“The place looked like it had no future,” said Dr. Fred Okuku, a Ugandan who trained as a medical student during Mbidde’s last years at the UCI.

Mbidde didn’t have the money to hire doctors, so he recruited third-year medical students from Makerre University to work in exchange for hands-on training. Like Cheever so many years earlier, Okuku often worked the night shift, tending to patients after everyone else left. Unlike Cheever, Okuku didn’t feel he was at the dawn of miraculous new treatments, at least not then. Few patients could afford to pay for medicine, even if there were drugs to be had. Most arrived with such advanced cancers that treatment would have come too late anyway.

“We saw a lot of children die,” Okuku said. “Every patient, children especially, that we lost caused us lots of emotions.”

Okuku agreed to train there simply because the workload was so great he knew he would get lots of clinical practice. But like so many other doctors and nurses who would come to work at the UCI for little or no pay, he felt profoundly moved by how much he was needed. And though he never expected this to happen, he fell in love with the place.

That was how he came to be at the UCI for the formation of a new alliance between U.S. and Ugandan researchers.

"I wouldn't have gone into cancer if I hadn't gone to Uganda," said Dr. Mac Cheever, shown here as a 25-year-old medical student in Kampala.

Photo courtesy of Dr. Mac Cheever

Key allies

When Fred Hutch’s Dr. Corey Casper, now 44, first came to Uganda in 2004, he, like Cheever, was drawn to the UCI. It was no longer the site of game-changing research and treatment, as it had been more than 30 years earlier when Cheever was there. But the history — and the promise —remained. The challenge was to bring it back.

Hartwell, then president and director, "supported the vision of attacking cancer in Africa," said Corey.

Two years later, Casper joined the faculty and then took over the program. By then they'd also been joined by Dr. Jackson Orem, an esteemed Ugandan cancer researcher who trained at Makerere University in Kampala and Case Western Reserve University in Cleveland, Ohio, who replaced Mbidde as UCI director.

“The Fred Hutch Cancer Research Center is one of our very key allies for our plan of reinventing UCI, regaining the status that we used to have,” Orem told visitors to the UCI last summer.

Cancer causes more deaths in low- and middle-income countries than malaria, tuberculosis and HIV combined. Yet few governments, organizations or scientists were aware of this, much less working on research, prevention or treatment. The alliance aimed to change that.

It offered fellowships to young Ugandan doctors to study at Fred Hutch and the University of Washington so that they might return to the UCI to treat patients and do research. Where there was once only one oncologist at the UCI, now there are more than a dozen physicians, eight of them Hutch-trained oncologists. Another 300 Ugandan scientists and 40 Ugandan doctors have undergone shorter trainings in Kampala.

The research program continues and now includes Kaposi sarcoma, Burkitt and other non-Hodgkin lymphomas, cervical cancer, breast cancer and Hodgkin lymphomas. About 30 projects have been completed, and more than 7,000 Ugandans have taken part in studies.

Private grants allowed the alliance to add clinical care to research and training, starting with a pilot project on Burkitt lymphoma, with innovations that are being adopted by other UCI teams. Today the decade-long alliance is held up by the NCI as a model for research, training and patient care in low-income countries.

“It’s been a long, long journey here — all the suffering we went through, all the death we saw,” Okuku said. “All those things we talked about in those days and thought would never come to pass — now here we are.”

To Mika, the historian, it is the partnership between the two centers that makes the UCI-Fred Hutch alliance so successful — and so unusual, especially on the part of U.S. institutions.

“It took humility to recognize that there were tremendous Ugandan clinicians on the ground, this untapped human resource that just needed to be groomed,” she said. “They didn’t have the opportunity to train at a center of excellence, so [Fred Hutch researchers] said, ‘Let’s train them at a center of excellence.”

And when so many developed countries lure trained health care workers away from Africa to help with their own shortages, she pointed out, the UCI-Hutch alliance is giving caregivers and researchers skills to take home.

From the beginning of the alliance, a new building was seen as an essential part of the plan. Instead of a hodgepodge of 40-year-old bungalows, the alliance would have a suitable home for high-quality research, effective care and proper training.

‘I’ve always wanted to go back”

In recent years, Linda Cheever, who is married to the Hutch’s Mac Cheever, has become involved in the Rotary Club’s Malaria Partners program, which also works to eradicate Burkitt lymphoma. Her current involvement – she leads trips to Uganda for donors and others – and Cheever’s earlier time there sealed the case for going to Kampala for the opening of the new UCI-Fred Hutch Cancer Centre.

In the intervening years, Cheever has been present for many more firsts: Back in Seattle as a young researcher, he got to train under Dr. E. Donnall Thomas, whose pioneering work on bone marrow transplants cured patients of leukemia when nothing else did. Now he is involved in immunotherapy, which, by leveraging the immune system, could potentially treat other cancers once seen as incurable and do so in ways that are less toxic than radiation or chemotherapy. Once again, he is working on the cutting edge of medicine.

It all started in Uganda.

Funding for the Burkitt Lymphoma Project comes from the National Cancer Institute, the Burkitt’s Lymphoma Fund for Africa, the Martin-Fabert Foundation and individual donors.

Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.

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